1. Field of the Invention
The present invention relates to optically active epoxy compounds and processes for their production.
2. Discussion of Background
The optically active epoxy compounds and optically active (2S, 3R)-2,3-epoxypropionic acid derivatives having a substituent at the 3-position, of the present invention, are compounds useful as intermediates for the preparation of pharmaceuticals or agricultural chemicals. Further, the present invention relates to a β-halogenoketone derivative, a process for its production and a process for producing an enone derivative employing it.
A 3-halogenopropane derivative having substituents at 1,3-positions and 2-propen-1-one having substituents at 1,3-positions, of the present invention, are compounds useful as intermediates for the preparation of pharmaceuticals or agricultural chemicals.
Further, the present invention relates to a process for reproducing an optically active 2,3-epoxy-3-propionic acid having a substituents at 3-position and its ester.
The optically active 2,3-epoxypropionic acid having a substituent at 3-position and its ester, of the present invention, are compounds useful as intermediates for the preparation of pharmaceuticals or agricultural chemicals, as mentioned above.
As an asymmetric epoxidation reaction, an asymmetric epoxidation reaction of trans-allyl alcohol is known wherein titanium tetraisopropoxide and an optically active diethyl tartarate are employed, and tert-butyl hydroperoxide is further employed (e.g. K. B. Sharpless, et. al, J. Am. Chem. Soc. 109, 5765 (1987)).
Further, as a process for producing 2,3-epoxy-3-cyclohexylpropionic acid, a method is known wherein cis-2,3-epoxy-4-phenyl-butan-1-ol is oxidized by means of RuO4 to produce optically active cis-2,3-epoxy-4-phenyl-butanoic acid (e.g. K. B. Sharpless, et. al, J. Org. Chem. 50, 1560 (1985) and K. B. Sharpless, et. al, J. Org. Chem. 46, 3936 (1981)).
Further, as a process for producing 2,3-epoxy-4-methylpentanoic acid or 2,3-epoxyheptanoic acid, a method is known wherein the corresponding allyl alcohol is subjected to asymmetric epoxidation by using titanium tetraisopropoxide and an optically active diethyl tartarate and further using tert-butyl hydroperoxide, followed by oxidation to the carboxylic acid by means of RuO4 (e.g. JP-A-2002-80441).
The conventional asymmetric epoxidation reaction was not satisfactory as an industrial production process. For example, in the conventional asymmetric epoxidation reaction of trans-allyl alcohol, a large amount of an oxidizing agent was present in the reaction system at the time of the reaction, whereby it was a process accompanying a danger of explosion, etc. in the production in a large amount, although there would be no problem in the production in a small amount, and as such, it could hardly be regarded as an industrial production process.
1-Phenyl-3-cyclohexyl-2-propen-1-one is disclosed in various literatures (e.g. JP-A-11-80036).
Further, it is known that 1-phenyl-3-hydroxy-3-cyclohexylpropan-1-one can be obtained by a reaction of cyclohexanecarboxyaldehyde with acetophenone (e.g. International Patent Publication No. 02/041984).
Further, it is known that a 3-hydroxy-1-carbonyl compound (an aldol) formed by a by a common reaction of an aldehyde with a ketone, readily undergoes a dehydration reaction by an acid or a base to form an α, β-unsaturated ketone or an α,β-unsaturated ester (Herbert O. House, “Modern Synthetic Reactions Second Edition” (1972) W. A. Benjamin, Inc. p. 632–637).
In the conventional process, by-products were likely to be formed depending on the conditions in the resulting 1-phenyl-3-cyclohexyl-2-propen-1-one, and in order to obtain the desired product in high purity, precision purification by e.g. silica gel column chromatography was required, and thus, such could not hardly be regarded as an industrial production process.
As a process for producing optically active (2S,3R)-2,3-epoxy-3-cyclohexylpropionic acid, a method is, for example, known wherein, as mentioned above, 3-cyclohexyl-2-propen-1-ol is asymmetrically oxidized by tert-butyl hydroperoxide in the presence of optically active diethyl tartarate and titanium tetraisopropoxide (e.g. K. B. Sharpless, et. al, J. Am. Chem. Soc. 109, 5765 (1987)) to obtain optically active (2S,3R)-2,3-epoxy-3-cyclohexylpropan-1-ol, followed by oxidation by butenyl tetraoxide to obtain the desired optically active (2S,3R)-2,3-epoxy-3-cyclohexylpropionic acid (e.g. K. B. Sharpless, et. al, J. Org. Chem. 50, 1560 (1985) and K. B. Sharpless, et. al, J. Org. Chem. 46, 3936 (1981)).
Further, as a process for producing an optically active α,β-epoxycarboxylate by asymmetrical hydrolysis, a method has been reported which employs a lipase of α, β-epoxycarboxylate wherein the substituent at the β-position is aromatic (e.g. JP-A-3-15398) or a linear alkyl group (e.g. JP-A-5-276966), but no application to an α,β-epoxycarboxylate wherein the substituent at the β-position is a cyclic alkyl group such as a cyclohexyl group, has been known.
As mentioned above, the conventional process by an organic synthesis was not satisfactory as an industrial process for producing optically active (2S,3R)-2,3-epoxypropionic acids having a substituent at the 3-position.
Further, as a process for producing an optically active α,β-epoxycarboxylate by asymmetric hydrolysis, a process has not been known which employs a lipase of an α,β-epoxycarboxylate wherein the substituent at the β-position is a cyclic alkyl group such as a cyclohexyl group. Further, no case has been known to isolate an epoxy carboxylate wherein the steric configuration is (2S,3R), and in order to obtain a (2S,3R)-α,β-epoxycarboxylate, it was necessary to isolate (2S,3R)-α, β-epoxycarboxylic acid, followed by reesterification.